Pathophysiology

Diseases such as gastroenteritis, diabetic ketoacidosis or Addison’s disease cause their

own specific changes in fluid and electrolyte balance, but there are non-specific changes which
occur in response to any form of injury or inflammation, which have important implications for
management, particularly of surgical patients. Response to injury In the 1930’s, Cuthbertson
described the metabolic changes, which occur in response to injury (including surgery and
sepsis), as an increase in metabolic rate and protein breakdown to meet the requirements for
healing. These changes were later shown to be due to neuroendocrine and cytokine changes and
to occur in three phases.
The ebb or shock phase is brief and is modified by resuscitation. This gives way to the
flow or catabolic phase, the length and intensity of which depends on the severity of injury and
its complications. As inflammation subsides, the convalescent anabolic phase of rehabilitation
begins. In parallel with these metabolic changes there are changes in water and electrolyte
physiology. During the flow phase, there is an increase in ADH and aldosterone secretion
leading to retention of salt and water with loss of potassium. These changes are exacerbated by
any reduction in blood or ECF volume. The normal, if somewhat sluggish, ability to excrete an
excess salt and water load is further diminished , leading to ECF expansion and oedema. The
response to injury also implies that oliguria is a normal response to surgery, and does not
necessarily indicate the need to increase the administration of salt and water or plasma expanders
unless there are also indications of intravascular volume deficit, e.g. from postoperative bleeding.
Salt and water retention after injury can be seen as nature’s way of trying to protect the ECF and
circulating volume at all costs. It also explains why sick patients can be so easily overloaded
with excessive salt and water administration during the flow phase. Since water as well as salt is
retained, it is also easy to cause hyponatraemia by giving excess water or hypotonic fluid. It is
important, therefore, to administer crystalloids, not only in the correct volume but also in the
appropriate concentration. In the presence of the response to injury, the kidneys are unable to
correct for errors in prescribing.
The convalescent phase of injury is not only characterised by the return of anabolism but
also by a returning capacity to excrete any excess salt and water load that has been accumulated.
These periods have been termed the ‘sodium retention phase’ and the ‘sodium diuresis phase’ of
injury.

Transcapillary escape rate of albumin

The response to injury, stress and sepsis also results in an increase in the size of the pores in the
capillary membrane and the transcapillary escape rate of albumin increases from about 5%/h in
health to 13- 15%/h. This phenomenon can last from several hours to days. Albumin leaks out
from the intravascular compartment into the interstitial space and along with it, water and
sodium are also drawn into the interstitial space. This results in a net contraction of the
intravascular compartment and expansion of the interstitial space (Fig. 4). As the return of
albumin to the circulation via the lymphatics is unchanged, the net result is an intravascular
hypovolaemia with oedema.
 Figure 4: Effects of an increase in the transcapillary escape rate of albumin.

Potassium
K+ losses after surgery, sepsis and trauma are not only secondary to increased excretion, but also
to protein and glycogen catabolism. As intracellular protein is broken down and its constituent
amino acids are released from cells, so intracellular negative charges are lost and K+, with its
balancing positive charges, passes out into the ECF to be excreted. In situations where
catabolism is extreme and renal function is impaired, the outflow of K+ from the cells may
exceed the kidney’s capacity to excrete it, causing dangerous hyperkalaemia. Conversely, in the
convalescent phase, as net intracellular protein and glycogen anabolism is restored, the cells take
up K+ again and the patient’s potassium intake has to be increased or else hypokalaemia will
develop.

Conclusion
Appropriate fluid therapy depends on an understanding of the underlying physiology and
pathophysiology and a consideration not only ofexternal but internal fluid balance.
Definitions
Much confusion in the diagnosis and treatment of fluid and electrolyte disorders is caused
by loose and ambiguous terminology. The term ‘dehydration’, for example, meaning lack of
water, is often used carelessly and imprecisely to include salt and water lack or, even more
confusingly, intravascular fluid depletion. We therefore make a plea for the use of precise
diagnostic terms, which indicate clearly the
deficit or excess and the treatment required.
Anabolism – the synthesis of large molecules from small ones, e.g. protein from amino
acids or glycogen from glucose.
Catabolism – the breakdown of large molecules into small ones, e.g. protein to amino
acids or glycogen to glucose.
Total body water (TBW) – percentage of body composition consisting of water,
approximately 60% of body weight, less in obesity and more in infants.
Intracellular fluid (ICF) volume – that part of the TBW contained within the cells,
approximately 40% of body weight and 2/3rds of TBW. Muscle cells contain 75% water and fat
cells have <5% water.
Extracellular fluid (ECF) volume – that portion of the TBW outside the cells,
approximately 20% of body weight and 1/3rd of TBW, sustained osmotically mainly by sodium.
Interstitial fluid volume – that portion of the ECF outside the circulation and surrounding
the cells.

Intravascular fluid volume

– the total blood volume consisting of red and white cells and plasma. May be estimated at
approximately 5-7% of the body weight.
– the plasma volume is that part of the ECF contained within the circulation and supported
oncotically by the plasma proteins, separated from the interstitial fluid by the capillary
membrane. Comprises approximately 3-4% of the body weight.
– the effective circulatory volume refers to that part of the ECF that is in the arterial system
(normally 700 ml in a 70 kg man – 10% of body weight) and is effectively perfusing the
tissues.

Salt – in chemistry this is used to describe a whole family of compounds such as MgSO4,
FeSO4, CaCl2, etc. but colloquially and in clinical practice it has come to mean NaCl, and that
usage will be followed in this book.

Electrolyte – a substance whose components dissociate in solution into positively (cation) and
negatively (anion) charged ions. For example, sodium chloride in solution (saline), dissociates
into Na+ and Cl–.Other electrolytes of physiological importance include Ca2+, Mg2+, K+, PO42-,
etc. Glucose is not an electrolyte since it does not dissociate in solution. At all times the total
number of positive charges balances the number of negative charges to achieve electrical
neutrality.

Dehydration – the term ‘dehydration’ strictly means lack of water, yet it is also used colloquially
to mean lack of salt and water or even more loosely to describe intravascular volume depletion.
The terms ‘wet’ and ‘dry’ are applied to patients with similarly imprecise meaning. We make a
plea for confining the use of dehydration to mean ‘water lack’ and for using unambiguous terms
such as ‘salt and water depletion’, ‘blood loss’, ‘plasma deficit’, and so forth, since these are
clear diagnoses indicating logical treatments. It may, however, be used legitimately to describe
fluid deficit from sweating, remembering that a litre of sweat contains up to 50 mmol Na+. This
may require salt as well as water replacement under tropical conditions.